Document Detail


Derivation of HLA-A11/Kb transgenic mice: functional CTL repertoire and recognition of human A11-restricted CTL epitopes.
MedLine Citation:
PMID:  9366399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.
Authors:
J Alexander; C Oseroff; J Sidney; P Wentworth; E Keogh; G Hermanson; F V Chisari; R T Kubo; H M Grey; A Sette
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  159     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-11-25     Completed Date:  1997-11-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4753-61     Citation Subset:  AIM; IM    
Affiliation:
Cytel Corporation, San Diego, CA 92121, USA. alexander@cytelcorp.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytotoxicity, Immunologic / genetics
Epitopes, T-Lymphocyte / genetics*,  immunology
H-2 Antigens / genetics*
HLA-A Antigens / genetics*,  immunology
Humans
Influenza A virus / immunology
Lymphocyte Activation / genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic / genetics,  immunology*
Peptides / immunology,  metabolism
Protein Binding / genetics,  immunology
Recombinant Fusion Proteins / biosynthesis,  genetics*,  immunology
Species Specificity
T-Lymphocytes, Cytotoxic / immunology*
Transgenes / immunology
Grant Support
ID/Acronym/Agency:
N01-AI-45241/AI/NIAID NIH HHS; R01 AI20001/AI/NIAID NIH HHS; RR00833/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Epitopes, T-Lymphocyte; 0/H-2 Antigens; 0/HLA-A Antigens; 0/HLA-A11; 0/Peptides; 0/Recombinant Fusion Proteins
Comments/Corrections
Erratum In:
J Immunol 1999 Mar 1;162(5):3104

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